Regulation of Stationary Phase in Escherichia coli

大肠杆菌固定相的调节

• 批准号: 7578838
• 负责人: Thomas J. Silhavy
• 金额: $ 28.53万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7578838
• 关键词: Address; Animals; Bacteria; Bacteria sigma factor KatF protein; Biochemical; Biology; Carbon; Cells; Computing Methodologies; Enterobacteriaceae; Escherichia; Escherichia coli; Genetic; Genetic Translation; Light; Mediating; Metabolism; Microbe; Molecular; Nitrogen; Nutrient; Orphan; Pathogenesis; Pathway interactions; Peptide Hydrolases; Phase; Phosphorus; Process; Proteins; Regulation; Sigma Factor; Signal Transduction; Source; Starvation; Testing; deprivation; genetic regulatory protein; insight; metabolomics; pathogen; response

DESCRIPTION (provided by applicant): Enteric bacteria such as Escherichia coli spend most of their lifetimes starved for one or more essential nutrients. To survive environmental challenges under starvation conditions these bacteria enter a non-growing state called stationary phase. The master regulator of stationary phase is the alternate primary sigma factor RpoS. In rapidly growing cells RpoS levels are low because the orphan response regulator SprE (RssB) targets RpoS for degradation by the CIpP/X protease. We have discovered that when bacteria are starved for carbon, RpoS levels increase because RpoS degradation stops. Starvation for phosphorus also results in elevated levels of RpoS, but in this case levels are elevated because of an increase in rpoS mRNA translation. In contrast starvation for nitrogen does not cause an increase in RpoS levels; rather, RpoS activity is increased. We propose a combination of genetic, biochemical, metabolomic, and computational methods to identify the key signaling and effector molecules that mediate these diverse responses to nutrient deprivation. Since RpoS is known to be important for the pathogenesis of certain bacteria, a detailed understanding of how bacteria enter and exit stationary phase may reveal chinks in the armor of these pathogens. In addition, because the pathways of central metabolism are conserved throughout biology, we think that the signals that trigger transition to a non-growing state may be conserved as well. Thus insights gained in bacteria may shed light on similar processes in eukaryotic microbes, and perhaps animal cells as well.

描述（由申请人提供）：大肠杆菌等肠道细菌在其一生的大部分时间里都在缺乏一种或多种必需营养素。为了在饥饿条件下生存的环境挑战，这些细菌进入称为静止期的非生长状态。固定相的主调节器是备用主西格玛因子 RpoS。在快速生长的细胞中，RpoS 水平较低，因为孤儿反应调节因子 SprE (RssB) 的目标是 RpoS 被 CIpP/X 蛋白酶降解。我们发现，当细菌缺乏碳时，RpoS 水平会增加，因为 RpoS 降解停止。缺磷也会导致 RpoS 水平升高，但在这种情况下，水平升高是因为 rpoS mRNA 翻译增加。相反，氮饥饿不会导致 RpoS 水平增加；相反，RpoS 活动有所增加。我们提出结合遗传、生化、代谢组学和计算方法来识别介导这些对营养剥夺的不同反应的关键信号传导和效应分子。由于已知 RpoS 对某些细菌的发病机制很重要，因此详细了解细菌如何进入和退出静止期可能会揭示这些病原体盔甲中的缝隙。此外，由于中枢代谢途径在整个生物学中是保守的，我们认为触发向非生长状态转变的信号也可能是保守的。因此，在细菌中获得的见解可能有助于了解真核微生物（也许还有动物细胞）中的类似过程。